RANDOM BIOPSY AFTER NEGATIVE COLPOSCOPY

A single random biopsy at the transformation zone increases the detection rate of high-grade cervical disease by approximately 20% in women who have a negative colposcopy, a new post hoc analysis shows.

Warner Huh, MD, from the University of Alabama Hospital, Birmingham, and colleagues found that a single random biopsy taken at the squamocolumnar junction in women in whom no lesions were visualized at colposcopy detected 20.9% of cervical intraepithelial neoplasias (CIN) grade 2 or worse and 18.9% of CIN grade 3 or worse in women involved in the Addressing the Need for Advanced HPV Diagnostics (ATHENA) trial.

This additional disease was detected in both human papillomavirus 16 (HPV16)- and HPV18-positive women as well as in 12 other high-risk HPV-positive women, the authors write.

The study was published online September 5 in Obstetrics & Gynecology.

"At the present time in the United States, there is no 'standard' for colposcopy regarding the number of biopsies that should be taken. Clinical practice can range from taking one biopsy from the worst visible lesion to performing four quadrant biopsies, irrespective of the presence or absence of colposcopy abnormalities," the authors observe. "Thus, it is highly challenging to understand the contribution of random biopsies in clinical practice when no true clinical standard exists for colposcopy."

"It is reasonable to do this," David Chelmow, MD, professor and chair, obstetrics and gynecology, Virginia Commonwealth University Medical Center, Richmond, told Medscape Medical News.

"But the big question is: Is a random biopsy going to lead to more cervical cancers being prevented? And we don't know the answer to that question yet."

ATHENA Trial

The ATHENA trial screened more than 47,000 women with cytology and high-risk HPV DNA genotyping. Colposcopy was performed in all women with abnormal cytology or positive HPV results.

The current analysis involved the overall population of women in ATHENA who were aged 25 years and older and who had valid HPV test and cervical biopsy results.

This group was further stratified into those with abnormal cytology results and those in whom cytology was negative for intraepithelial lesions or malignancy.

A total of 6.9% (2839 women) of the ATHENA cohort underwent a random biopsy, and 2796 of them had valid biopsy results. More than 90% of the random biopsies were negative or normal; 5.7% were graded CIN 1, 1.3% were CIN 2, 1.4% were CIN 3, and 0.14% were CIN 3 or worse.

When stratified by HPV status, 13.3% of HPV16- or HPV18-associated disease was detected with the random biopsy compared with only 3.5% of detected disease attributable to the other 12 high-risk HPV genotypes.

The highest percentage of high-grade disease was identified in women between the ages of 25 and 29 years, the authors add.

"These results point to the surprisingly high rate of additional disease detection achieved with random biopsies," the researchers conclude. "[T]he absolute risk of lesions detected in the absence of visible lesions in women testing positive for HPV 16 or 18 justifies taking a random biopsy in these populations in accordance with proposed risk assessment models."

Dr. Chelmow said other studies have also demonstrated that additional cervical disease is detected with additional biopsies, "so it's not so much that the finding is new but this study breaks it down by HPV types and stratifies where that yield comes from."

The US Food and Drug Administration has already approved the HPV genotype tests for primary HPV screening, he noted.

"Right now, we are waiting to see what the major societies are going to do in terms of whether they recommend the new HPV test or not," Dr. Chelmow observed.

In the meantime, Dr. Chelmow noted both that most colposcopists follow current guidelines regarding how to best manage both abnormal cytology and abnormal HIV tests and that different algorithms are followed depending on what is detected on cytology and what is visible on colposcopy.

"The other question here is, if you do find a high-grade lesion, would you then go ahead and treat it because that's going to result in many more people being treated?" Dr. Chelmow said. "And as the authors themselves asked, is treating these tiny lesions that you can't see on colposcopy going to prevent additional cervical cancer?"

This research was supported by Roche Molecular Systems. One coauthor has received consulting fees and research funding from Sanofi, Roche Molecular Systems, and Becton Dickinson and has also served as an advisor to GSK and Qiagen. Another coauthor has served as a consultant or expert pathologist in HPV-related vaccine or clinical diagnostic trials for Merck, Roche, Hologic/GenProbe, BD, Quigen, Cepheid, and Inovio. Two coauthors are employees of Roche Molecular Systems. The other authors and Dr. Chelmow have disclosed no relevant financial relationships.

Obstet Gynecol. Published online September 5, 2014. Abstract